Long-term consequences of chronic HIV infection and its treatment, particularly disturbances of bone metabolism, are emerging concerns given the growing numbers of older adults living with HIV. Insulin-like growth factor-I (IGF-I) and its binding proteins (IGFBPs) are among the most important regulators of bone function. Alterations in the IGF system have been described in patients with osteoporosis, wasting syndrome, and lipodystrophy - disorders which are prevalent among HIV-infected individuals. Opioid users possess multiple risk factors for bone disease, and recently opioid use has been independently associated with reductions in cross-sectional studies of bone mineral density in HIV-infected and at-risk older men and women. Furthermore IGF-I, IGFBP-1, and IGFBP-3 are produced in the liver, and drug users have multiple risks for liver disease, including hepatitis C virus infection, which may potentially affect the IGF axis (e.g. through decreased hepatic production). The pathogenesis of loss of BMD in HIV-infected individuals, whether or not they are opioid users, is unclear at this point. The proposed study will examine whether the IGF-axis helps explain the linkage between drug use and HIV infection and the development of disorders of bone and fat metabolism. The Specific Aims of this study are (1) To determine the association between IGF-I and changes in bone mineral density (BMD) in relation to HIV infection and opioid use among men and women participating in a prospective cohort study;(2) To determine the association of IGFBP family members with HIV and opioid use and their individual relation to bone mineral density changes in women and men participating in a prospective cohort study;and (3) To determine the association between IGF-I and fat redistribution in relation to HIV infection among men and women participating in a prospective cohort study. In order to evaluate the association between IGF-I and changes in bone mineral density (BMD) in relation to HIV infection and opioid use among men and women, the proposed study will take advantage of the existing data collected as part of two NIDA funded cohorts designed specifically to evaluate metabolic complications of HIV among drug using women and men, as part of which participants underwent serial bone densitometry and data collection on demographics, sexual and drug-using behaviors and medical history. Assays will be performed to measure IGF-I, IGFBP-1, and IGFBP-3. With large numbers of subjects under study, extended follow-up time, and the availability of this extensive database that includes detailed information on drug use history, as well as predictors of HIV morbidity and antiretroviral therapy, high quality prospective clinical research can be conducted in a cost effective and timely manner. Despite the substantial overlap between opioid use and HIV, longitudinal data which examine bone mineral density in drug using populations affected by HIV are lacking. The proposed study will expand the understanding of the relationship between HIV and bone mineral density, and will address the role of drug use in the pathogenesis of bone loss, about which very little is known.